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He lost his wife to a state of unresponsiveness following a tragic accident. Over the past two years, he’s tried everything to bring her back—including an experimental first in the use of psychedelics.
On September 24th, 2022, David was driving to pick up his wife when he heard a loud crash followed by screams. He got out of the car and ran toward the noise. There he saw his wife, Sarah, lying on the ground.
Sarah was crossing the street when she was hit by a car driving at about 30 miles per hour. The impact left her with severe brain damage and a fractured pelvis.
She was unresponsive and remained in a coma for 17 days before she began responding to instructions to move parts of her body, including her hands and toes. But as weeks and months went by, her condition swung between periods of fleeting awareness and complete unresponsiveness.
“There ensued this endless nightmare,” says David.
For people whose awareness is impaired or completely absent, collectively known as “disorders of consciousness,” treatments are limited. Since the accident, David, a digital marketer, has dedicated his life to caring for Sarah and doing whatever he can to revive her consciousness, including extensive research and consulting with experts about the latest treatments. He also plays the guitar for his wife, reads books to her, bathes her, and uses a wheelchair to take her on strolls through the park.
Sarah is among as many as 300,000 people in states of severely impaired consciousness caused primarily by accidents, strokes, and lack of oxygen to the brain. Around 4,000 new cases are documented annually in the United States. With only few experimental therapies available, thousands of families are desperate for solutions.
“The stakes couldn’t be higher,” says David. “There’s nothing I wouldn’t do to help her. If I could give her my own neurons, I would.”
Every day, for more than 550 days, David has been meticulously noting Sarah’s condition and the impact of treatments: stimulants, sleeping pills, ADHD medications, supplements, cognitive enhancers known as “nootropics," and techniques to arouse the brain, including transcranial direct-current stimulation. He’s also tried various recommended nutrients administered through a feeding tube: shots of espresso, scoops of matcha, mushroom-based powders, liquid turmeric, lemon juice, and Chinese acupuncture tea.
Nothing has helped.
But one drug gave him hope: psilocybin, the mind-altering ingredient in magic mushrooms. After consulting with Olivia Gosseries, a neuroscientist at the University of Liège and research associate for the National Fund for Scientific Research in Belgium, David realized that using psychedelics wasn’t a fringe idea, but rather an experiment worth trying.
“I got really curious about the prospect of psilocybin,” says David.
Psychedelics hold promise for treating severe psychiatric conditions, including treatment-resistant depression, post-traumatic stress disorder, and anxiety disorder. More than 200 registered clinical trials have explored the effects of psychedelics on various mental disorders, and at least 160 are currently in progress worldwide.
But the use of traditional psychedelics in patients with disorders of consciousness would be a first.
“We’ve never tried, we just don’t know,” says Gosseries, who is now leading one of the primary efforts to test psychedelics in these patients in Belgium.
Gosseries’s own study, which has been approved by a university and national-level ethics committee in Belgium, involves using psilocybin and ketamine—a widely used medical anesthetic that has psychedelic effects at low doses—in patients with disorders of consciousness.
According to Paolo Cardone, the doctoral student leading the research, out of the three patients who have received ketamine to date, two kept their eyes open significantly longer than usual and showed less muscle rigidity, suggesting promising improvements in their overall condition. Still, they couldn't communicate and scientists cannot be sure there was greater awareness.
A team at Imperial College London will be submitting an ethics application for a similar study using dimethyltryptamine, or DMT—a powerful, natural psychedelic compound found in many plants and animal species—on patients with disorders of consciousness.
These efforts are controversial. Giving psychedelics to patients in vulnerable states raises thorny scientific and ethical questions surrounding consent, the potential to induce traumatizing experiences, and the legalities of such a procedure.
“I’m glad they’re doing it,” says Robin Carhart-Harris, professor of neurology and psychiatry at the University of California San Francisco, who first outlined some of these questions in a 2019 proposal paper. But, he adds, “it is fraught with ethical sensitivities.”
Ideally, such an experiment would happen in a controlled, clinical setting to ensure safety and rigorous scientific standards, says Gosseries. But clinical trials using psilocybin won’t start before 2025 and, for people like David and countless others desperate to bring back their loved ones, waiting isn’t an option.
“While I'm interested in helping science, I'm most interested in waking my wife up,” says David.
At the heart of this scientific initiative is the notion of brain “complexity.” In neuroscience, complexity is a measure of how diverse and unpredictable brain activity is. Brain activity that is uniform and fixed is described as having low complexity. Activity that is scattered, unpredictable, and rapidly changing from one state to the next is considered to be highly complex.
Over the past two decades, a series of experiments have shown that brains of people who are awake and healthy tend to be higher in this complexity measure than those of people who are in dreamless sleep, sedated, or have a disorder of consciousness.
The findings have led scientists to hypothesize that complexity acts as a reliable indicator for how conscious someone is, making it a particularly powerful tool for assessing the conscious level of individuals who can't communicate but who might still be aware, as with patients with disorders of consciousness.
The way complexity is measured in the brain varies, but generally entails either recording electrical or magnetic signals on the surface of a patient's brain and using mathematical tools to decipher the complexity of these signals. Or, stimulating the brain with a device, recording how large groups of brain cells react, and using computational methods to quantify how diverse and unpredictable these responses are.
“It's a little bit like you take a bell, you hit it with a hammer, and you're listening to the reverberations,” says Christof Koch, a computational neuroscientist at the Allen Institute for Brain Science in Seattle.
In 2017, using magnetic signals, scientists found for the first time that psychedelics like ketamine, LSD, and psilocybin, could raise healthy people’s brain complexity levels beyond those observed during regular day-to-day life. The results were replicated in similar studies using different kinds of brain technologies, psychedelic drugs, and measures of brain complexity.
The science behind how psychedelics could restore consciousness in patients with disorders of consciousness is still not well understood. Some scientists point to how psychedelics open up a critical window during which the brain reorganizes itself and forms new long-term connections—an ability known as “neuroplasticity.” Some of these newly-built connections could help rewire patients’ brains in unpredictable ways and lead them to emerge from unconsciousness or have greater bodily control, scientists say.
Psychedelics can help patients suffering from PTSD, anxiety, and depression, because this rewiring can help reconfigure how these memories, fears, and other emotions are encoded and processed.
“But if you're not forming memories and you have no sense of self, then in what way are these drugs going to be helpful?” notes Eric Spier, medical director of the Brain Injury Program at Craig Hospital in Colorado, who treated Sarah when she was admitted.
Ultimately, the logic driving these scientific initiatives is the correlation that exists between brain complexity and conscious level. But correlation is not causation, and it’s possible that the rise in complexity seen when under the influence of psychedelics is actually pointing to brain activity unrelated to growing conscious awareness, says Anil Seth, professor of computational neuroscience at the University of Sussex, and investigator on the 2017 study.
For example, it could be capturing the multi-sensorial richness of their experience during the trip, the random firing of neurons, or unwanted, reflexive bodily movements.
“There’s many missing knowledge gaps,” says Seth.
Still, the results led scientists to wonder: could psychedelic’s ability to boost complexity levels be used to awaken patients with disorders of consciousness?
For David, there was only one way to find out.
On August 25, 2023, exactly 336 days following Sarah’s tragic accident, David, who is based in Colorado where psychedelic mushrooms are decriminalized, obtained a tincture of distilled liquid psilocybin. He had already given Sarah low and moderate doses of the drug over the course of several months and it had a “remarkable" affect in her bodily movements.
This time, however, he would go all in, using the equivalent of 2.5 grams—a dose high enough to provoke a powerful psychedelic experience and which is often used in clinical trials for therapeutic purposes. At this dose, both Gosseries and Carhart-Harris said an awakening was theoretically possible.
The legalities of what David was about to do were unclear. Colorado’s decriminalization of certain psychedelics in 2022 means that psilocybin is easy to access and magic mushrooms can be grown and consumed. But whether David was crossing a line by giving Sarah the drug, when she could not consent, was not obvious.
David felt that if there was even a slim chance that psychedelics could awaken Sarah, he would take the risk.
Sarah sat in her wheelchair and wore a helmet-like headset with cables sprouting out of the back of her head, feeding into a laptop. The headset, a commercial-grade piece of equipment called a WAVi, measured the electrical activity from her brain and was going to be recorded and analyzed by Frank Palermo, medical director of the Colorado-based company, WAVi Co., which focuses on medical equipment manufacturing. Palermo also describes himself as a physiatrist specializing in neurorehabilitation, as he does in a video of him posted on Neurologic Life, a company that markets medical devices, including WAVi.
The idea was to measure Sarah's brain waves before and during the experiment at short intervals to see how her complexity levels fluctuated. Palermo could monitor the activity while he was recording, observing the brainwaves on his laptop screen.
Present in the room with David and Palermo was John Kaditus, a close friend of David and someone who previously worked as a paramedic. Gosseries was also virtually present that day on an iPad placed above Sarah, although only as an observer and in a strictly unofficial capacity.
There were many reasons to be worried: Many bioethicists have warned about problems surrounding lack of consent, the possibility of experiencing a “bad trip,” and questions about what would happen in a situation of partial awakening—where Sarah becomes lucid enough to understand her predicament but is unable to do anything about it.
“This is terrifying,” Kaditus said at the time.
David mixed the dark brown liquid psilocybin with water and fed it through Sarah's feeding tube in her abdomen. Just 10 minutes later, Sarah’s body underwent a sudden and frightening transformation: Her legs raised into the air off of her wheelchair and her eyes and mouth opened wide. Her hands, normally limp and unable to grasp objects, were now extended. David placed his hand in hers and felt an unusually tight grip.
He checked her blood pressure and it was at 158/97, considered very high, especially for Sarah who tended to have low blood pressure. Some 30 minutes later her blood pressure rose even further.
“She looked like she was on some kind of crazy ride through the universe,” says David. “And it was scary because I thought: What the hell did I just do to her?”
Sarah’s body fluctuated between this rigid posture and a more relaxed pose for the next two hours. Her body was clearly undergoing something unusual and her brain signals, measured by the headset she wore, shot through the roof compared to baseline.
"Her beta brain waves are incredible!” wrote David in his notes based on Palermo’s reaction. Beta waves are fast, low-amplitude waves that are generally characteristic of an aroused and actively engaged mind. "Her brain is indeed fired up! Look at this!”
Palermo later confirmed that, for about an hour, Sarah's brainwaves showed a fourfold increase in their frequency and this suggested she was alert and potentially agitated.
Gosseries and her team is currently analyzing the brain data to see how it might translate in terms of complexity levels and what Sarah may have been experiencing.
Despite these promising brain markers, Sarah showed no clear signs of awareness: When asking her to look up, she did not respond. And when David placed a mirror in front of her and moved it up and down to see if her eyes could track it, she would not.
About two to three hours later, the drugs began to wear off, her blood pressure stabilized, and Sarah began to look more calm. She was moved into her bed in a different room surrounded by plants, soft light, music, and lit incense. David tested her again using standardized methods he had been taught by Gosseries to see if there were any improvements. Nothing significant.
“It was a very, very, long and stressful day. Unless I see some sign of improvement over the coming days, I do not think I will put her through this again. I had to try. Now what?” he wrote in his medical notes that evening.
David never did see any lasting improvements after the psychedelic experience and dropped the idea of using psilocybin again.
Two months after the procedure was carried out, the U.S. Food and Drug Administration issued a warning letter to David Oakley, chief executive officer of WAVi Co., which states that, upon inspection of the firm, they found multiple regulatory violations including with both a headset used to measure electrical activity and software used to decode recordings.
In response, Oakley noted that the letter does not strictly refer to its FDA-cleared WAVi headset or software to scan brain electrical activity, which, he says, have been validated and are cleared for both research and clinical use.
“WAVi is cleared to market and sell the headset and nothing in the warning letter suggests otherwise,” Oakley wrote in an email.
The results of that August procedure on Sarah were “not what we were hoping for,” says Gosseries, “but she might still have been more conscious without us being able to see it.”
Whichever way one interprets these findings, what’s clear is that Sarah is not necessarily representative of a wider community of patients in disorders of consciousness. Such patients vary wildly in their types of injuries, recovery rates, and responsiveness to treatments.
“There's a saying in brain injury that once you've seen one brain injury, you’ve seen one brain injury,” says Spier, the Craig Hospital medical director.
Sarah’s type of brain injury, focused in and around the thalamus and brainstem, is not uncommon among patients with disorder of consciousness. Scientists have shown that the thalamus acts as a hub, receiving information from your senses and sending this to key brain regions for further processing. The brainstem also plays a fundamental role in sustaining vital functions like breathing and heart rate. If these sites get damaged, the risks of suffering severe brain damage or falling into a coma are substantial.
One theory for why Sarah didn’t show great improvements after psilocybin is that the logic underpinning the experiment is misguided, says John Whyte, founding director of the Moss Rehabilitation Research Institute in Pennsylvania. The low level of complexity found in patients with disorders of consciousness might best be understood as the loss of critical parts of a person’s brain architecture, including brain cells, networks, and entire regions, as a result of serious brain injury, he says.
“The fundamental issue is this: is this low complexity the cause of unconsciousness or the result of profound brain damage?” notes Whyte.
If the brain is damaged, then rewiring using psychedelics when core parts of its machinery are missing simply won’t work, he says. Instead, Whyte suggests first trying to identify the minimal core structures necessary to sustain consciousness. Once that is done experts can start targeting treatments on patients whose brain machinery looks like it could be successfully rebooted.
“If we want to test whether the drug really works, we need to test it on a group of people who could respond to it in principle, not people who couldn't,” Whyte adds.
For decades, neuroscientists and philosophers have sought to do exactly that: identify what they’ve termed the “neural correlates of consciousness.” There is currently no scientific consensus but two candidate regions have been proposed. One involves the posterior regions of the neocortex, an area at the back of the brain in a “hot zone" where many brain regions overlap. The other is the prefrontal cortex, a frontal region sometimes known as the brain's “executive center.”
Other ways to recreate a brain architecture involve more experimental methods like generating new brain cells by injecting stem cells into the fluid that circulates around the brain, a strategy that, at one point, David was seriously considering.
But, more than 550 days and dozens of different treatments later, David has lost all hope of getting his wife back. Keeping Sarah alive in this dire state, he says, is doing more harm than good.
In the next few weeks, David has decided to proceed with end of life treatment.
“It's absolutely devastating as my darling is the light of my life.”
Can psychedelics treat people with a severe brain injury? – National Geographic
